Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

Jung, Byung-Jin; Yoo, Hwan-Sic; Shin, Sooyoung; Park, Young-Joon; Jeon, Sang-Min

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자료유형: 학술저널

저자정보: Jung, Byung-Jin (College of Pharmacy, Ajou University) Yoo, Hwan-Sic (College of Pharmacy, Ajou University) Shin, Sooyoung (College of Pharmacy, Ajou University) Park, Young-Joon (College of Pharmacy, Ajou University) Jeon, Sang-Min (College of Pharmacy, Ajou University)

저널정보: 한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제26권 제1호

발행연도: 2018.1

수록면: 57 - 68 (12page)

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Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

#NRF2 #KEAP1 #NRF2 inhibitors #Cancer

참고문헌 (130)

참고문헌 신청

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Ahren, B. / 2008 / Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes / Expert Opin. Emerg. Drugs 13:593~607

Alam, M. M. / 2017 / Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2 / J. Biol. Chem. 292:7519~7530

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Camp, N. D. / 2012 / Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein / J. Biol. Chem. 287:6539~6550

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